Objective: To examine evidence for the effectiveness of computer-assisted cognitive-behavior therapy (CCBT) for depression in primary care and assess the impact of therapist-supported CCBT versus self-guided CCBT. Methods: A search for randomized studies of CCBT compared to control groups for treating depression in primary care settings was conducted using Ovid MEDLINE, PsycINFO, PubMed, and Scopus. We extracted the following information from the studies that met inclusion criteria: mean depression rating scale scores before and after treatment, number of patients, type of control group and CCBT program, therapist support time and method of support, and treatment completion rate. Meta-analyses compared differences between posttreatment mean scores in each condition, as well as mean scores at follow-up. Study quality and possible bias also were assessed. Results: Eight studies of CCBT for depression in primary care met inclusion criteria. The overall effect size was g = 0.258, indicating a small but significant advantage for CCBT over control conditions. Therapist support was provided in 4 of the 8 studies. The effect size for therapist-supported CCBT was g = 0.372—a moderate effect. However, the effect size for selfguided CCBT was g = 0.038, indicating little effect. Conclusions: Implementation of therapist-supported CCBT in primary care settings could enhance treatment efficiency, reduce cost, and improve access to effective treatment for depression. However, evidence to date suggests that self-guided CCBT offers no benefits over usual primary care.